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Open AccessArticle

Recurrent Stimulation of Natural Killer Cell Clones with K562 Expressing Membrane-Bound Interleukin-21 Affects Their Phenotype, Interferon-γ Production, and Lifespan

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya, Moscow 117997, Russia
Center for Childhood Cancer and Blood Disorders, The Research Institute, Nationwide Children’s Hospital, Columbus, OH 43205, USA
Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(2), 443;
Received: 30 November 2018 / Revised: 27 December 2018 / Accepted: 16 January 2019 / Published: 21 January 2019
(This article belongs to the Special Issue The Interleukins in Health and Disease)
A pattern of natural killer cell (NK cell) heterogeneity determines proliferative and functional responses to activating stimuli in individuals. Obtaining the progeny of a single cell by cloning the original population is one of the ways to study NK cell heterogeneity. In this work, we sorted single cells into a plate and stimulated them via interleukin (IL)-2 and gene-modified K562 feeder cells that expressed membrane-bound IL-21 (K562-mbIL21), which led to a generation of phenotypically confirmed and functionally active NK cell clones. Next, we applied two models of clone cultivation, which differently affected their phenotype, lifespan, and functional activity. The first model, which included weekly restimulation of clones with K562-mbIL21 and IL-2, resulted in the generation of relatively short-lived (5–7 weeks) clones of highly activated NK cells. Levels of human leukocyte antigen class II molecule—DR isotype (HLA-DR) expression in the expanded NK cells correlated strongly with interferon-γ (IFN-γ) production. The second model, in which NK cells were restimulated weekly with IL-2 alone and once on the sixth week with K562-mbIL21 and IL-2, produced long-lived clones (8–14 weeks) that expanded up to 107 cells with a lower ability to produce IFN-γ. Our method is applicable for studying variability in phenotype, proliferative, and functional activity of certain NK cell progeny in response to the stimulation, which may help in selecting NK cells best suited for clinical use. View Full-Text
Keywords: NK cell clones; IL-2; K562-mbIL21; membrane-bound IL-21 NK cell clones; IL-2; K562-mbIL21; membrane-bound IL-21
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Streltsova, M.A.; Erokhina, S.A.; Kanevskiy, L.M.; Grechikhina, M.V.; Kobyzeva, P.A.; Lee, D.A.; Telford, W.G.; Sapozhnikov, A.M.; Kovalenko, E.I. Recurrent Stimulation of Natural Killer Cell Clones with K562 Expressing Membrane-Bound Interleukin-21 Affects Their Phenotype, Interferon-γ Production, and Lifespan. Int. J. Mol. Sci. 2019, 20, 443.

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